Risk of second malignant neoplasms after childhood leukemia and lymphoma:: An international study

Background Survivors of childhood leukemia and lymphoma experience high risks of second malignant neoplasms. We quantified such risk using a large dataset from 13 population-based cancer registries. Methods The registries provided individual data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring in children aged 0-14 years and on subsequent second malignant neoplasms for different time periods from 1943 to 2000. Risks of second malignant neoplasms were assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (Cls), using the incidence rates in the general populations covered by the registries as a reference. Cumulative absolute risks were also calculated. Results A total of 133 second malignant neoplasms were observed in 16540 patients (12731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin lymphomas) after an average follow-up of 6.5 years. The most frequent second malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% Cl = 5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% Cl = 4.30 to 17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% Cl = 8.60 to 35.7); the most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5, 95% Cl = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% Cl = 7.66 to 45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% Cl = 12.5 to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer (six cases, SIR = 40.4, 95% Cl = 14.8 to 88.0) and brain cancer (four cases, SIR = 6.97, 95% Cl = 1.90 to 17.9). Cumulative incidence of any second malignant neoplasm was 2.43% (95% Cl = 1.09 to 3.78), 12.7% (95% Cl = 8.29 to 17.2), and 2.50% (95% Cl = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, respectively. Conclusions This population-based study provides, to our knowledge, the most precise and up-to-date estimates for relative and absolute risks of second malignant neoplasms after childhood leukemia and lymphoma.